NeuroNex Technology Hub: Enhanced resolution for 3DEM analysis of synapses across brain regions and taxa

作为NSF国家神经科学研究基础设施的一部分，这个神经技术中心将开发新的方法来更详细地检查大脑。三维电子显微镜（3DEM）有助于揭示大脑细胞之间微小连接的作用。 然而，3DEM的影响受到数据分析速度的限制。 这个神经技术中心将改进3DEM仪器，以更详细地收集信息，开发更好的算法来处理信息，并将工作流程与高性能计算联系起来，以大大提高知识发现的速度。这些创新和能力将通过积极的方法培训和开放获取新的软件和数据与科学界分享。通过这个神经技术中心，3DEM将成为国家神经科学研究基础设施的一部分。为了帮助解决理解大脑的重大科学挑战，该项目将在包括人类在内的几种不同哺乳动物物种中应用改进的3DEM方法，以确定相似性和差异，以及它们与行为，学习和记忆的关系。这个神经技术中心的动机是理解突触的挑战，神经元间的微小通信点。突触尺寸、连接性和亚细胞内容在物种之间的差异是未知的，但需要确定模型系统是否代表人类大脑功能。目前的方法受到分辨率、低效的数据收集和分析瓶颈的限制。针对这些挑战，该项目将：（1）开发在透射模式下操作的扫描电子显微镜上的同时多探测器和倾斜层析成像。附加硬件和软件将轴向分辨率从45 nm提高到10 nm（或更低），同时保持1-2 nm的面内分辨率。(2)集成自动化和交互式工具，加快并改进对大数据量中突触的分析。增强的分辨率将增加数据量，但通过产生更多的各向同性图像来减少主要的图像处理困难。(3)将增强型电子显微镜（EM）与高性能计算相结合，以提高吞吐量;以便于吸收现有细胞类型和大脑数据库的方式传播图像，元数据，分析和软件;并提供一个开发3DEM社区的场所。(4)应用这项新技术对小鼠、大鼠和人类的海马体和类似的皮质部分进行成像。 该NeuroTechnology Hub奖由生物科学理事会新兴前沿部门和计算机和信息科学理事会高级网络基础设施办公室共同资助，作为BRAIN计划和NSF理解大脑活动的一部分。

As part of the NSF National Research Infrastructure for Neuroscience, this Neurotechnology Hub will develop new approaches to examine the brain in greater detail. Three-dimensional electron microscopy (3DEM) has helped reveal new insights into the role of tiny connections between cells in the brain. However, 3DEM has been limited in impact by the rate of data analysis. This Neurotechnology Hub will improve the 3DEM instrumentation to collect information in greater detail, develop better algorithms to process the information, and link the workflows with high performance computing to greatly increase the rate of knowledge discovery. These innovations and capabilities will be shared with the scientific community through active training on the approach, and through open access to the new software and data. By way of this Neurotechnology Hub, 3DEM will become part of the national infrastructure for neuroscience research. To help address the grand scientific challenge of understanding the brain, this project will apply the improved 3DEM approach across several different mammalian species including humans to identify similarities and differences, and their relationship to behavior, learning, and memory.This Neurotechnology Hub is motivated by challenges in understanding synapses, the tiny points of inter-neuronal communication. The variance in synapse dimensions, connectivity, and subcellular content across species is simply not known, yet required to determine whether model systems represent human brain functions. Current approaches are limited by resolution, inefficient data collection, and analysis bottlenecks. Addressing these challenges, the project will: (1) Develop simultaneous multi-detector and tilt-tomography on the scanning electron microscope operating in the transmission mode. Add-on hardware and software will improve axial resolution from 45 to 10 nm (or less), while maintaining in-plane resolution of 1-2 nm. (2) Integrate automated and interactive tools that speed and improve analysis of synapses in large data volumes. The enhanced resolution will increase data volume but reduce major image processing difficulties by producing more isotropic images. (3) Integrate the enhanced electron microscopy (EM) with high performance computing to increase throughput; to disseminate images, metadata, analyses, and software in a way that facilitates uptake into existing cell type and brain databases; and to provide a venue to develop 3DEM communities. (4) Apply the new technology to image hippocampus and comparable parts of cortex in mice, rats, and humans. This NeuroTechnology Hub award is co-funded by the Division of Emerging Frontiers within the Directorate for Biological Sciences and the Office of Advanced Cyberinfrastructure within the Directorate for Computer and Information Sciences, as part of the BRAIN Initiative and NSF's Understanding the Brain activities.